Patients report well-being as they are treated with phototherapy. We investigated hormone parameters and psychological well-being after phototherapy in a placebo-controlled study. A total of 77 patients with dermatological conditions and 22 healthy volunteers were divided into four groups. The patients received phototherapy either on the whole body or only on hands and/or feet. The volunteers were given either whole-body phototherapy or placebo light. Serum or plasma samples were analysed for cortisol, calcium, magnesium, phosphate, TSH, T(4), T(3) and 25-hydroxyvitamin D, and urine samples for cortisol. Patients and volunteers answered a questionnaire before and 6 weeks after phototherapy/placebo light. Psychiatric ratings were performed according to the Comprehensive Psychopathological Self-rating Scale for Affective Syndromes, a self-report version of which has been transformed to correspond to the Montgomery-Asberg Depression Rating Scale (MADRS). In the patients who received whole-body irradiation, we observed a significant improvement in both MADRS score and cognitive-symptom score after the completion of phototherapy. We also observed a significantly higher level of 25-hydroxyvitamin D after phototherapy, but no difference in the other hormone parameters. Whole-body phototherapy of patients with dermatological conditions results in improved well-being and significantly higher levels of 25-hydroxyvitamin D in serum.